title: Contribution of IL-17-producing gamma delta T cells to the efficacy of anticancer chemotherapy.
abstract: By triggering immunogenic cell death, some anticancer compounds, including anthracyclines and oxaliplatin, elicit tumor-specific, interferon-γ-producing CD8(+) αβ T lymphocytes (Tc1 CTLs) that are pivotal for an optimal therapeutic outcome. Here, we demonstrate that chemotherapy induces a rapid and prominent invasion of interleukin (IL)-17-producing γδ (Vγ4(+) and Vγ6(+)) T lymphocytes (γδ T17 cells) that precedes the accumulation of Tc1 CTLs within the tumor bed. In T cell receptor δ(-/-) or Vγ4/6(-/-) mice, the therapeutic efficacy of chemotherapy was compromised, no IL-17 was produced by tumor-infiltrating T cells, and Tc1 CTLs failed to invade the tumor after treatment. Although γδ T17 cells could produce both IL-17A and IL-22, the absence of a functional IL-17A-IL-17R pathway significantly reduced tumor-specific T cell responses elicited by tumor cell death, and the efficacy of chemotherapy in four independent transplantable tumor models. Adoptive transfer of γδ T cells restored the efficacy of chemotherapy in IL-17A(-/-) hosts. The anticancer effect of infused γδ T cells was lost when they lacked either IL-1R1 or IL-17A. Conventional helper CD4(+) αβ T cells failed to produce IL-17 after chemotherapy. We conclude that γδ T17 cells play a decisive role in chemotherapy-induced anticancer immune responses.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1015, France.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Ma
authors.forename: Laetitia
authors.initials: L
authors.lastname: Aymeric
authors.forename: Clara
authors.initials: C
authors.lastname: Locher
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Mattarollo
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Delahaye
authors.forename: Pablo
authors.initials: P
authors.lastname: Pereira
authors.forename: Laurent
authors.initials: L
authors.lastname: Boucontet
authors.forename: Lionel
authors.initials: L
authors.lastname: Apetoh
authors.forename: François
authors.initials: F
authors.lastname: Ghiringhelli
authors.forename: Noëlia
authors.initials: N
authors.lastname: Casares
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Lasarte
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: Koichi
authors.initials: K
authors.lastname: Ikuta
authors.forename: Bernard
authors.initials: B
authors.lastname: Ryffel
authors.forename: Kamel
authors.initials: K
authors.lastname: Benlagha
authors.forename: Antoine
authors.initials: A
authors.lastname: Tesnière
authors.forename: Nicolas
authors.initials: N
authors.lastname: Ibrahim
authors.forename: Julie
authors.initials: J
authors.lastname: Déchanet-Merville
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chaput
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Smyth
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
authors.forename: Laurence
authors.initials: L
authors.lastname: Zitvogel
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology / Q000502:physiology; D020381:Interleukin-17 / Q000276:immunology / Q000502:physiology*; D053759:Interleukin-23 / Q000276:immunology / Q000502:physiology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology / Q000502:physiology*; D012513:Sarcoma, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000503:physiopathology; D015398:Signal Transduction / Q000276:immunology / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000502:physiology*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D020381:Interleukin-17; D053759:Interleukin-23; D016692:Receptors, Antigen, T-Cell, gamma-delta; D004317:Doxorubicin; D007371:Interferon-gamma